What is Antiphospholipid Syndrome

7/21/2019 What is Antiphospholipid Syndrome

http://slidepdf.com/reader/full/what-is-antiphospholipid-syndrome 1/6

What is antiphospholipid syndrome?

The antiphospholipid syndrome is a disorder of the immune system that is characterized by

excessive clotting of blood and/or certain complications of pregnancy (premature miscarriages,

unexplained fetal death, or premature birth) and the presence of antiphospholipid antibodies

(cardiolipin or lupusanticoagulant antibodies) in the blood. Patients with antiphospholipid

syndrome have developed abnormal symptoms while having antiphospholipid antibodies that are

detectable with blood testing.

ntiphospholipid syndrome is also called phospholipid antibody syndrome. ntiphospholipid

syndrome has been referred to as !ughes syndrome in honor of the doctor who first described it.

"t is important to note that antiphospholipid antibodies can also be found in the blood of

individuals without any disease process. "n fact, antiphospholipid antibodies have been reported

in approximately #$ of the normal population. !armless antiphospholipid antibodies can be

detected in the blood for a brief period occasionally in association with a wide variety of

conditions, including bacterial, viral (hepatitis, !"%), and parasite (malaria) infections. &ertain

drugs can cause antiphospholipid antibodies to be produced in the blood, including antibiotics,

cocaine, hydralazine,procainamide, and 'uinine.

evertheless, the antiphospholipid antibody (a protein) is not considered a normal blood protein

and has been found in patients to be associated with a number of illnesses. These illnesses

include abnormal clotting (thrombosis) of arteries (stroe, infarction) and/or veins (phlebitis),

premature miscarriages (spontaneous abortions), abnormally low blood platelet counts

(thrombocytopenia), purplish mottling discoloration of the sin (livedo reticularis), migraine

headaches, and a rare form of inflammation of the nervous tissue of the brain or spinal cord,

called transverse myelitis. ntiphospholipid antibodies have also been detected in over half ofpatients with the immune disease systemic lupus erythematosus.

*esearchers are recently also finding that there are patients with slowly progressive memory

problems and patients with a form of +atypical multiple sclerosis+ and antiphospholipid antibodies

detectable in their blood.

hat laboratory tests can support the diagnosis of antiphospholipid

syndrome-

Patients with the antiphospholipid syndrome can have a variety of antibodies to molecules calledphospholipids in their blood. These antibodies include %*/*P* (a syphilis testthat can be

falsely positive in these patients), lupus anticoagulant, prolonged PTT, and cardiolipin antibody.

s mentioned above, the anticardiolipin antibody has also been found in patients with the

immune disease systemic lupus erythematosus, which is characterized by the production of a

variety of abnormal antibodies.

hat causes antiphospholipid syndrome-

The cause of antiphospholipid syndrome is not completely nown. ntiphospholipid antibodies

reduce the levels of annexin %, a protein that binds phospholipids and has potent clot0blocing(anticoagulant) activity. The reduction of annexin % levels is thought to be a possible mechanism

http://www.medicinenet.com/script/main/art.asp?articlekey=33915



















































underlying the increased tendency of blood to clot and the propensity to pregnancy loss

characteristic of the antiphospholipid syndrome.

ntiphospholipid antibodies, such as anticardiolipin, have also been associated with decreased

levels of prostacyclin, a chemical that prevents the clumping together of normal blood clotting

elements called platelets.

!ow is antiphospholipid syndrome treated-

The treatment of patients with anticardiolipin syndrome has substantially evolved since they were

discovered to be clinically important in the mid01234s. 5ach manifestation of the antiphospholipid

syndrome, and each individual patient with the condition, is treated uni'uely.

6ecause many of the features of illness with anticardiolipin syndrome are associated with an

abnormal grouping of normal blood clotting elements (platelets), treatment is often directed

toward preventing clotting by thinning the blood. Patients with this disorder have an abnormal

tendency to formblood clots (thrombosis). The abnormal blood clotting can affect the function of

virtually any organ. 7edications that thin (anticoagulate) the blood, such as heparin (!ep0oc,

i'uaemin) and warfarin (&oumadin) (powerful blood thinners), are used for treatment. spirin

has an affect on platelets that inhibits their grouping (aggregation) and has also been used in low

doses to thin the blood of selected patients. &ortisone0related medications, such asprednisone,

have been used to suppress the immune activity and inflammation in patients with certain

features of the condition. 8or patients with systemic lupus erythematosus who also have

antiphospholipid syndrome, hydroxychloro'uine (Pla'uenil) has been reported to add some

protection against blood clotting.

9ther reported treatments include the use of intravenous gamma globulin for selected patients

with histories of premature miscarriage and those with low blood0clotting elements (platelets)

during pregnancy. *ecent research studies, however, suggest that intravenous gamma globulin

may be no more effective than combination aspirin and heparin treatment.

hat is catastrophic antiphospholipid syndrome-

&atastrophic antiphospholipid syndrome is a variant of antiphospholipid syndrome that is

characterized by blocage of many blood vessels throughout the body. s a result of catastrophicantiphospholipid syndrome, many organs can be affected, including the sin, lungs, brain, heart,

idneys, and bowels. &atastrophic antiphospholipid syndrome is treated with anticoagulation,

corticosteroids (cortisone medication), andplasmapheresis (plasma exchange).

&atastrophic antiphospholipid syndrome is rare, affecting less than 1$ of those with

antiphospholipid syndrome. &atastrophic antiphospholipid syndrome is sometimes referred to as

sherson:s syndrome after the researcher who described it in the early 1224s.

ntiphospholipid ;yndrome t <lance

• ntiphospholipid syndrome is an immune disorder that can affect virtually any organ.




















o 3bat:obatan lain : nter#eron al#a Buinine amo>iillin

Predisposisi geneti!

o Hubungan !eluarga/ Hubungan !eluarga dengan orang yang menderita antiphospholipid syndrome memili!i

!emung!inan besar memili!i antibody anti#os#olipid. Suatu penelitian menggambar!an #re!uensi sebesar 665.

o HLA/ Suatu penelitian terbaru menemu!an sebuah !aitan antara antibodi anti!ardiolipin dan se!elompo!

individu dengan gen:gen HLA tertentu termasu! D=8$6 D= (paling banya! pada orang Hispani) dan D=7(terutama pada orang !ulit putih).

ntiphospholipid syndrome (P;) is a disorder that manifests clinically as recurrent venous or arterial

thrombosis and/or fetal loss. &haracteristic laboratory abnormalities in P; include persistently

elevated levels of antibodies directed against membrane anionic phospholipids (ie, anticardiolipin

=a&> antibody, antiphosphatidylserine) or their associated plasma proteins, predominantly beta0#

glycoprotein " (apolipoprotein !)? or evidence of a circulating anticoagulant.

7ultiple terms for P; exist. @nfortunately, some synonyms can be confusing. upus anticoagulant() syndrome, for example, is misleading because patients with P; may not necessarily

have systemic lupus erythematosus (;5) and is associated with thrombotic rather than

hemorrhagic complications. "n an attempt to avoid further confusion, P; is currently the preferred

term for the clinical syndrome (as described below).

;ome patients with P; have no evidence of any definable associated disease, while, in other

patients, P; occurs in association with ;5 or another rheumatic or autoimmune disorder.

Traditionally, these have been referred to as primary or secondary P;, respectively. &urrently,

however, the preferred terminology is P; with or without associated rheumatic disease. lthough

antiphospholipid (aP) antibodies are clinically lined to P;, whether they are involved in the

pathogenesis or are an epiphenomenon is unclear. (@p to A$ of healthy individuals are nown to

have aP antibodies.)

"n P;, the homeostatic regulation of blood coagulation is altered? however, the mechanisms ofthrombosis are not yet defined. 9ne hypothesis postulates a defect in cellular apoptosis, whichexposes membrane phospholipids to the binding of various plasma proteins, such as beta0#glycoprotein ". 9nce bound, a phospholipid0protein complex is formed and a neoepitope is uncovered,which subse'uently becomes the target of autoantibodies. *ecent evidence suggests that oxidizedbeta0# glycoprotein " is able to bind to and activate dendritic cells in a manner similar to activationtriggered by Toll0lie receptor B (T*0B), which could amplify the production of autoantibodies. =1, #>

9ther proposed mechanisms for the hypercoagulable effect of aP antibodies, which may or may notdepend on beta0# glycoprotein ", include the followingC

• Production of antibodies against coagulation factors, including prothrombin, protein &, protein

;, and annexins

• ctivation of platelets to enhance endothelial adherence

• ctivation of vascular endothelium, which, in turn, facilitates the binding of platelets and

monocytes

• *eaction of antibodies to oxidized low0density lipoprotein, thus predisposing to

atherosclerosis and myocardial infarction (7")&omplement activation has been increasingly recognized as a possible significant role in thepathogenesis of P;. 5merging evidence from murine models suggests that P0mediatedcomplement activation may be a primary event in pregnancy loss. =D>

&linically, the series of events that leads to hypercoagulability and recurrent thrombosis can affectvirtually any organ system, including the followingC

http://emedicine.medscape.com/article/332244-overview






• Peripheral venous system (deep venous thrombosis =%T>)

• &entral nervous system (cerebrovascular accident =&%>, sinus thrombosis)

• !ematologic (thrombocytopenia, hemolytic anemia)

• 9bstetric (pregnancy loss, eclampsia)

• Pulmonary (pulmonary embolism =P5>, pulmonary hypertension)

•

ermatologic (livedo reticularis, purpura, infarcts/ulceration)• &ardiac (ibman0;acs valvulopathy, 7")

• 9cular (amaurosis, retinal thrombosis)

• drenal (infarction/hemorrhage)

• 7usculoseletal (avascular necrosis of bone)

Epidemiology

8re'uency

United States

The actual fre'uency of P; in the general population is unnown. 9ne to A$ of healthy individuals

have aP antibodies. a& antibodies tend to be found more fre'uently in elderly persons? thus,

positive titer results should be interpreted with caution in this population. aP antibodies are found in

approximately D40B4$ of patients with ;5, but only about 14$ have P;. =B> pproximately half of

P; cases are not associated with another rheumatic disease. "n a study of 144 patients with

confirmed venous thrombosis and no history of ;5, a& antibodies were found in #B$ and in B$.

International

"nternational fre'uency is probably similar to @; fre'uency.

7ortality/7orbidity

• P; may contribute to an increased fre'uency of &%s or 7"s, especially in younger

individuals. &%s may develop secondary to in situ thrombosis or embolization that originates fromthe valvular lesions of ibman0;acs (sterile) endocarditis, which may be seen in patients with P;.&ardiac valvular disease may be severe enough to re'uire valve replacement. *ecurrent pulmonaryemboli or thrombosis can lead to life0threatening pulmonary hypertension.

• &atastrophic P; (&P;) is a rare, serious, and often fatal manifestation (mortality rate of

approximately A4$) characterized by multiorgan infarctions over a period of days to wees.

• ate spontaneous fetal loss (second or third trimester) is common? however, it can occur at

any time during pregnancy. *ecurrent early fetal loss (E 14 weesF gestation) is also possible.

*ace

• o defined racial predominance for primary P; has been documented, although ;5 is

more common in frican merican and !ispanic populations.

;ex










• female predominance has been documented, particularly for secondary P;. This parallels

the association of P; with ;5 and other connective0tissue diseases, which also have a femalepredominance.

ge

• P; is more common in young to middle0aged adults? however, it also manifests in children

and elderly people. isease onset has been reported in children as young as 3 months. "n aninternational registry of pediatric P; cases, patients without associated rheumatic disease wereyounger and had a higher fre'uency of arterial thrombotic events, whereas patients with associatedrheumatic disease were older and had a higher fre'uency of venous thrombotic events associatedwith hematologic and sin manifestations.=A>

Documents

What is Antiphospholipid Syndrome